A number of psychiatric conditions are linked to impulsive behaviour, including suicidal behaviour, addictive conditions such as drug, alcohol and gambling addiction, eating disorders, aggression, and self-mutilating behaviour. It has been estimated that in Europe, there were 15.5 million cases of addiction that required treatment in 2010, costing a total of €65.7 billion (Olesen et al.; European Journal of Neurology, 2012, 19, 155-162). Therefore, the prevalence and the societal and financial consequences of such disorders are substantial.
Lithium is currently one of the few pharmacological treatments that has some activity in impulsivity-related disorders. Lithium suffers from the problem of toxicity, its toxic level being only twice that of its therapeutic concentration. It requires frequent blood level monitoring which is inconvenient and expensive. It can also cause side effects such as polyurea, polydypsia, and kidney damage, in addition to interfering with thyroid function. It can also cause adverse interactions with other commonly known used drugs, which limits the clinical populations where it can be used.
The physiological basis for impulse control disorders is not clear. Although a link between lithium and inhibition of the enzyme inositol monophosphatase is thought to be responsible for its ability to treat bipolar disorder (Berridge et al., Cell, 1989, 59, 411-419), lithium itself has a diverse range of biochemical effects, which could also explain its high toxicity and side-effect profile (Atack et al., Trends in Neurosciences, 1995, 18(8), 343-349 and Medicinal Research Reviews, 1997, 17(2), 215-224).
Therefore, there is a need for alternative treatments for conditions related to impulsivity that are less toxic than lithium, can be used in a wider clinical population, and which have better compatibility with other commonly used drugs.